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Abstract:

Disclosed herein are methods and compositions for producing articular
repair materials and for repairing an articular surface. In particular,
methods for providing articular repair systems. Also provided are
articular surface repair systems designed to replace a selected area
cartilage, for example, and surgical tools for repairing articular
surfaces.

Claims:

1. A method of designing or selecting an articular implant for repairing
articular cartilage of a joint, the articular implant having an inner
surface for facing bone and an outer surface for facing a cavity of a
joint, the method including:obtaining an image of a joint, the image
including shape information of at least one of subchondral bone and
cartilage;deriving the shape of the at least one of subchondral bone and
cartilage from the image; anddesigning or selecting the articular implant
with both the inner and the outer surface of the implant based, at least
in part, on the derived shape, wherein the articular implant includes an
attachment mechanism for fixing the articular implant to the joint.

2. A method of providing a tool for surgery of a joint, the tool
comprising:obtaining an image of a joint, the image including shape
information of at least one of subchondral bone and cartilage;deriving
the shape of the at least one of subchondral bone and cartilage from the
image;deriving alignment information from the image; andproviding a
surgical tool including:a surface for engaging a substantially uncut
joint surface, the surface based, at least in part, on the derived shape
and the alignment information; andat least one guide for directing a
surgical instrument.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]This application is a continuation of U.S. Ser. No. 10/305,652,
filed Nov. 27, 2002, which in turn is a continuation-in-part of U.S. Ser.
No. 10/160,667, filed May 28, 2002, which in turn claims the benefit of
U.S. Ser. No. 60/293,488 entitled "METHODS To IMPROVE CARTILAGE REPAIR
SYSTEMS", filed May 25, 2001, U.S. Ser. No. 60/363,527, entitled "NOVEL
DEVICES FOR CARTILAGE REPAIR, filed Mar. 12, 2002 and U.S. Ser. Nos.
60/380,695 and 60/380,692, entitled "METHODS AND COMPOSITIONS FOR
CARTILAGE REPAIR," and "METHODS FOR JOINT REPAIR," filed May 14, 2002,
all of which applications are hereby incorporated by reference in their
entireties.

TECHNICAL FIELD

[0002]The present invention relates to orthopedic methods, systems and
prosthetic devices and more particularly relates to methods, systems and
devices for articular resurfacing.

BACKGROUND

[0003]There are various types of cartilage, e.g., hyaline cartilage and
fibrocartilage. Hyaline cartilage is found at the articular surfaces of
bones, e.g., in the joints, and is responsible for providing the smooth
gliding motion characteristic of moveable joints. Articular cartilage is
firmly attached to the underlying bones and measures typically less than
5 mm in thickness in human joints, with considerable variation depending
on joint and site within the joint. In addition, articular cartilage is
aneural, avascular, and alymphatic. In adult humans, this cartilage
derives its nutrition by a double diffusion system through the synovial
membrane and through the dense matrix of the cartilage to reach the
chondrocyte, the cells that are found in the connective tissue of
cartilage.

[0004]Adult cartilage has a limited ability of repair; thus, damage to
cartilage produced by disease, such as rheumatoid and/or osteoarthritis,
or trauma can lead to serious physical deformity and debilitation.
Furthermore, as human articular cartilage ages, its tensile properties
change. The superficial zone of the knee articular cartilage exhibits an
increase in tensile strength up to the third decade of life, after which
it decreases markedly with age as detectable damage to type II collagen
occurs at the articular surface. The deep zone cartilage also exhibits a
progressive decrease in tensile strength with increasing age, although
collagen content does not appear to decrease. These observations indicate
that there are changes in mechanical and, hence, structural organization
of cartilage with aging that, if sufficiently developed, can predispose
cartilage to traumatic damage.

[0005]Usually, severe damage or loss of cartilage is treated by
replacement of the joint with a prosthetic material, for example,
silicone, e.g. for cosmetic repairs, or metal alloys. See, e.g., U.S.
Pat. No. 6,383,228, issued May 7, 2002; U.S. Pat. No. 6,203,576, issued
Mar. 20, 2001; U.S. Pat. No. 6,126,690, issued Oct. 3, 2000. Implantation
of these prosthetic devices is usually associated with loss of underlying
tissue and bone without recovery of the full function allowed by the
original cartilage and, with some devices, serious long-term
complications associated with the loss of significant amount of tissue
and bone can include infection, osteolysis and also loosening of the
implant.

[0006]Further, joint arthroplasties are highly invasive and require
surgical resection of the entire or the majority of the articular surface
of one or more bones. With these procedures, the marrow space is reamed
in order to fit the stem of the prosthesis. The reaming results in a loss
of the patient's bone stock.

[0007]Osteolysis will frequently lead to loosening of the prosthesis. The
prosthesis will subsequently have to be replaced. Since the patient's
bone stock is limited, the number of possible replacement surgeries is
also limited for joint arthroplasty. In short, over the course of 15 to
20 years, and in some cases shorter time periods, the patients may run
out of therapeutic options resulting in a very painful, non-functional
joint.

[0009]Despite the large number of studies in the area of cartilage repair,
the integration of the cartilage replacement material with the
surrounding cartilage of the patient has proven difficult. In particular,
integration can be extremely difficult due to differences in thickness
and curvature between the surrounding cartilage and/or the underlying
subchondral bone and the cartilage replacement material.

[0010]Thus, there remains a need for methods and compositions for joint
repair, including methods and compositions that facilitate the
integration between the cartilage replacement system and the surrounding
cartilage.

SUMMARY

[0011]The present invention provides novel devices and methods for
replacing a portion (e.g., diseased area and/or area slightly larger than
the diseased area) of a joint (e.g., cartilage and/or bone) with a
non-pliable, non-liquid (e.g., hard) implant material, where the
implant--achieves a near anatomic fit with the surrounding structures and
tissues. In cases where the devices and/or methods include an element
associated with the underlying articular bone, the invention also
provides that the bone-associated element achieves a near anatomic
alignment with the subchondral bone. The invention also provides for the
preparation of an implantation site with a single cut.

[0013]In another aspect, the invention includes a method of making
cartilage repair material, the method comprising the steps of (a)
measuring the dimensions (e.g., thickness, curvature and/or size) of the
intended implantation site or the dimensions of the area surrounding the
intended implantation site; and (b) providing cartilage replacement
material that conforms to the measurements obtained in step (a). In
certain aspects, step (a) comprises measuring the thickness of the
cartilage surrounding the intended implantation site and measuring the
curvature of the cartilage surrounding the intended implantation site. In
other embodiments, step (a) comprises measuring the size of the intended
implantation site and measuring the curvature of the cartilage
surrounding the intended implantation site. In other embodiments, step
(a) comprises measuring the thickness of the cartilage surrounding the
intended implantation site, measuring the size of the intended
implantation site, and measuring the curvature of the cartilage
surrounding the intended implantation site. In other embodiments, step
(a) comprises reconstructing the shape of healthy cartilage surface at
the intended implantation site.

[0014]In any of the methods described herein, one or more components of
the articular replacement material (e.g., the cartilage replacement
material) are non-pliable, non-liquid, solid or hard. The dimensions of
the replacement material may be selected following intraoperative
measurements, for example measurements made using imaging techniques such
as ultrasound, MRI, CT scan, x-ray imaging obtained with x-ray dye and
fluoroscopic imaging. A mechanical probe (with or without imaging
capabilities) may also be used to selected dimensions, for example an
ultrasound probe, a laser, an optical probe and a deformable material.

[0015]In any of the methods described herein, the replacement material may
be selected (for example, from a pre-existing library of repair systems),
grown from cells and/or hardened from various materials. Thus, the
material can be produced pre- or post-operatively. Furthermore, in any of
the methods described herein the repair material may also be shaped
(e.g., manually, automatically or by machine), for example using
mechanical abrasion, laser ablation, radiofrequency ablation,
cryoablation and/or enzymatic digestion.

[0016]In any of the methods described herein, the articular replacement
material may comprise synthetic materials (e.g., metals, polymers, alloys
or combinations thereof) or biological materials such as stem cells,
fetal cells or chondrocyte cells.

[0017]In another aspect, the invention includes a method of repairing a
cartilage in a subject, the method of comprising the step of implanting
cartilage repair material prepared according to any of the methods
described herein.

[0018]In yet another aspect, the invention provides a method of
determining the curvature of an articular surface, the method comprising
the step of intraoperatively measuring the curvature of the articular
surface using a mechanical probe. The articular surface may comprise
cartilage and/or subchondral bone. The mechanical probe (with or without
imaging capabilities) may include, for example an ultrasound probe, a
laser, an optical probe and/or a deformable material.

[0019]In a still further aspect, the invention provides a method of
producing an articular replacement material comprising the step of
providing an articular replacement material that conforms to the
measurements obtained by any of the methods of described herein.

[0020]In a still further aspect, the invention includes a partial or full
articular prosthesis comprising a first component comprising a cartilage
replacement material; and a second component comprising one or more
metals, wherein said second component has a curvature similar to
subchondral bone, wherein said prosthesis comprises less than about 80%
of the articular surface. In certain embodiments, the first and/or second
component comprises a non-pliable material (e.g., a metal, a polymer, a
metal allow, a solid biological material). Other materials that may be
included in the first and/or second components include polymers,
biological materials, metals, metal alloys or combinations thereof.
Furthermore, one or both components may be smooth or porous (or porous
coated). In certain embodiments, the first component exhibits
biomechanical properties (e.g., elasticity, resistance to axial loading
or shear forces) similar to articular cartilage. The first and/or second
component can be bioresorbable and, in addition, the first or second
components may be adapted to receive injections.

[0021]In another aspect, an articular prosthesis comprising an external
surface located in the load bearing area of an articular surface, wherein
the dimensions of said external surface achieve a near anatomic fit with
the adjacent cartilage is provided. The prosthesis of may comprise one or
more metals or metal alloys.

[0022]In yet another aspect, an articular repair system comprising (a)
cartilage replacement material, wherein said cartilage replacement
material has a curvature similar to surrounding or adjacent cartilage;
and (b) at least one non-biologic material, wherein said articular
surface repair system comprises a portion of the articular surface equal
to, smaller than, or greater than, the weight-bearing surface is
provided. In certain embodiments, the cartilage replacement material is
non-pliable (e.g., hard hydroxyapatite, etc.). In certain embodiments,
the system exhibits biomechanical (e.g., elasticity, resistance to axial
loading or shear forces) and/or biochemical properties similar to
articular cartilage. The first and/or second component can be
bioresorbable and, in addition, the first or second components may be
adapted to receive injections.

[0023]In a still further aspect of the invention, an articular surface
repair system comprising a first component comprising a cartilage
replacement material, wherein said first component has dimensions similar
to that of adjacent or surrounding cartilage; and a second component,
wherein said second component has a curvature similar to subchondral
bone, wherein said articular surface repair system comprises less than
about 80% of the articular surface (e.g., a single femoral condyle,
tibia, etc.) is provided. In certain embodiments, the first component is
non-pliable (e.g., hard hydroxyapatite, etc.). In certain embodiments,
the system exhibits biomechanical (e.g., elasticity, resistance to axial
loading or shear forces) and/or biochemical properties similar to
articular cartilage. The first and/or second component can be
bioresorbable and, in addition, the first or second components may be
adapted to receive injections. In certain embodiments, the first
component has a curvature and thickness similar to that of adjacent or
surrounding cartilage. The thickness and/or curvature may vary across the
implant material.

[0024]In a still further embodiment, a partial articular prosthesis
comprising (a) a metal or metal alloy; and (b) an external surface
located in the load bearing area of an articular surface, wherein the
external surface designed to achieve a near anatomic fit with the
adjacent cartilage is provided.

[0025]Any of the repair systems or prostheses described herein (e.g., the
external surface) may comprise a polymeric material, for example attached
to said metal or metal alloy. Further, any of the systems or prostheses
described herein can be adapted to receive injections, for example,
through an opening in the external surface of said cartilage replacement
material (e.g., an opening in the external surface terminates in a
plurality of openings on the bone surface). Bone cement, therapeutics,
and/or other bioactive substances may be injected through the opening(s).
In certain embodiments, bone cement is injected under pressure in order
to achieve permeation of portions of the marrow space with bone cement.
In addition, any of the repair systems or prostheses described herein may
be anchored in bone marrow or in the subchondral bone itself. One or more
anchoring extensions (e.g., pegs, etc.) may extend through the bone
and/or bone marrow.

[0026]In any of the embodiments and aspects described herein, the joint
can be a knee, shoulder, hip, vertebrae, elbow, ankle, etc.

[0027]In another aspect, a method of designing an articular implant
comprising the steps of obtaining an image of a joint, wherein the image
includes both normal cartilage and diseased cartilage; reconstructing
dimensions of the diseased cartilage surface to correspond to normal
cartilage; and designing the articular implant to match the dimensions of
the reconstructed diseased cartilage surface or to match an area slightly
greater than the diseased cartilage surface is provided. The image can
be, for example, MRI, CT, ultrasound, digital tomosynthesis and/or
optical coherence tomography images. In certain embodiments,
reconstruction is performed by obtaining a parametric surface that
follows the contour of the normal cartilage. The parametric surface can
include control points that extend the contour of the normal cartilage to
the diseased cartilage and/or a B-spline surface. In other embodiments,
the reconstruction is performed by obtaining a binary image of cartilage
by extracting cartilage from the image, wherein diseased cartilage
appears as indentations in the binary image; and performing a
morphological closing operation (e.g., performed in two or
three-dimensions using a structuring element and/or a dilation operation
followed by an erosion operation) to determine the shape of an implant to
fill the areas of diseased cartilage.

[0028]In yet another aspect, described herein are systems for evaluating
the fit of an articular repair system into a joint, the systems
comprising one or more computing means capable of superimposing a
three-dimensional (e.g., three-dimensional representations of at least
one articular structure and of the articular repair system) or a
two-dimensional cross-sectional image (e.g., cross-sectional images
reconstructed in multiple planes) of a joint and an image of an articular
repair system to determine the fit of the articular repair system. The
computing means may be: capable of merging the images of the joint and
the articular repair system into common coordinate system; capable of
selecting an articular repair system having the best fit; capable of
rotating or moving the images with respect to each other; and/or capable
highlighting areas of poor alignment between the articular repair system
and the surrounding articular surfaces. The three-dimensional
representations may be generated using a parametric surface
representation.

[0029]In yet another aspect, surgical tool for preparing a joint to
receive an implant are described, for example a tool comprising one or
more surfaces or members that conform to the shape of the articular
surfaces of the joint (e.g., a femoral condyle and/or tibial plateau of a
knee joint). In certain embodiments, the tool comprises lucite and/or
silastic. The tool can be re-useable or single-use. In certain
embodiments, the tool comprises an array of adjustable, closely spaced
pins. In any embodiments described herein, the surgical tool may further
comprising an aperture therein, for example one or more apertures having
dimensions (e.g., diameter, depth, etc.) smaller or equal to one or more
dimensions of the implant and/or one or more apertures adapted to receive
one or more injectables. Any of the tools described herein may further
include one or more curable (hardening) materials or compositions, for
example that are injected through one or more apertures in the tool and
which solidify to form an impression of the articular surface.

[0030]In still another aspect, method of evaluating the fit of an
articular repair system into a joint is described herein, the method
comprising obtaining one or more three-dimensional images (e.g.,
three-dimensional representations of at least one articular structure and
of the articular repair system) or two-dimensional cross-sectional images
(e.g., cross-sectional images reconstructed in multiple planes) of a
joint, wherein the joint includes at least one defect or diseased area;
obtaining one or more images of one or more articular repair systems
designed to repair the defect or diseased area; and evaluating the images
to determine the articular repair system that best fits the defect (e.g.,
by superimposing the images to determine the fit of the articular repair
system into the joint). In certain embodiments, the images of the joint
and the articular repair system are merged into common coordinate system.
The three-dimensional representations may be generated using a parametric
surface representation. In any of these methods, the evaluation may be
performed by manual visual inspection and/or by computer (e.g.,
automated). The images may be obtained, for example, using a C-arm system
and/or radiographic contrast.

[0031]In yet another aspect, described herein is a method of placing an
implant into an articular surface having a defect or diseased area, the
method comprising the step of imaging the joint using a C-arm system
during placement of the implant, thereby accurately placing the implant
into a defect or diseased area.

[0032]These and other embodiments of the subject invention will readily
occur to those of skill in the art in light of the disclosure herein.

BRIEF DESCRIPTION OF THE FIGURES

[0033]The file of this patent contains at least one drawing executed in
color. Copies of this patent with color drawing(s) will be provided by
the Patent and Trademark Office upon request and payment of the necessary
fee.

[0034]FIG. 1 is a flowchart depicting various methods of the present
invention including, measuring the size of an area of diseased cartilage
or cartilage loss, measuring the thickness of the adjacent cartilage, and
measuring the curvature of the articular surface and/or subchondral bone.
Based on this information, a best fitting implant can be selected from a
library of implants or a patient specific custom implant can be
generated. The implantation site is subsequently prepared and the
implantation is performed.

[0035]FIG. 2 is a color reproduction of a three-dimensional thickness map
of the articular cartilage of the distal femur. Three-dimensional
thickness maps can be generated, for example, from ultrasound, CT or MRI
data. Dark holes within the substances of the cartilage indicate areas of
full thickness cartilage loss.

[0036]FIG. 3 shows an example of a Placido disc of concentrically arranged
circles of light.

[0037]FIG. 4 shows an example of a projected Placido disc on a surface of
fixed curvature.

[0038]FIG. 5 shows an example of a 2D color-coded topographical map of an
irregularly curved surface.

[0039]FIG. 6 shows an example of a 3D color-coded topographical map of an
irregularly curved surface.

[0040]FIG. 7 shows a reflection resulting from a projection of concentric
circles of light (Placido Disk) on each femoral condyle, demonstrating
the effect of variation in surface contour on the reflected circles.

[0041]FIG. 8A-H are schematics of various stages of knee resurfacing. FIG.
8A shows an example of normal thickness cartilage in the anterior,
central and posterior portion of a femoral condyle 800 and a cartilage
defect 805 in the posterior portion of the femoral condyle. FIG. 8B shows
an imaging technique or a mechanical, optical, laser or ultrasound device
measuring the thickness and detecting a sudden change in thickness
indicating the margins of a cartilage defect 810. FIG. 8C shows a
weight-bearing surface 815 mapped onto the articular cartilage. Cartilage
defect 805 is located within the weight-bearing surface 815. FIG. 8D
shows an intended implantation site (stippled line) 820 and cartilage
defect 805. The implantation site 820 is slightly larger than the area of
diseased cartilage 805. FIG. 8E depicts placement of an exemplary single
component articular surface repair system 825. The external surface of
the articular surface repair system 826 has a curvature similar to that
of the surrounding cartilage 800 resulting in good postoperative
alignment between the surrounding normal cartilage 800 and the articular
surface repair system 825. FIG. 8F shows an exemplary multi-component
articular surface repair system 830. The distal surface of the deep
component 832 has a curvature similar to that of the adjacent subchondral
bone 835. The external surface of the superficial component 837 has a
thickness and curvature similar to that of the surrounding normal
cartilage 800. FIG. 8G shows an exemplary single component articular
surface repair system 840 with a peripheral margin 845 substantially
non-perpendicular to the surrounding or adjacent normal cartilage 800.
FIG. 8H shows an exemplary multi-component articular surface repair
system 850 with a peripheral margin 845 substantially non-perpendicular
to the surrounding or adjacent normal cartilage 800.

[0042]FIG. 9, A through E, are schematics depicting exemplary knee imaging
and resurfacing. FIG. 9A is a schematic depicting a magnified view of an
area of diseased cartilage 905 demonstrating decreased cartilage
thickness when compared to the surrounding normal cartilage 900. The
margins 910 of the defect have been determined. FIG. 9B is a schematic
depicting measurement of cartilage thickness 915 adjacent to the defect
905. FIG. 9C is a schematic depicting placement of a multi-component
mini-prosthesis 915 for articular resurfacing. The thickness 920 of the
superficial component 923 closely approximates that of the adjacent
normal cartilage 900 and varies in different regions of the prosthesis.
The curvature of the distal portion of the deep component 925 is similar
to that of the adjacent subchondral bone 930. FIG. 9D is a schematic
depicting placement of a single component mini-prosthesis 940 utilizing
fixturing stems 945. FIG. 9E depicts placement of a single component
mini-prosthesis 940 utilizing fixturing stems 945 and an opening 950 for
injection of bone cement 955. The mini-prosthesis has an opening at the
external surface 950 for injecting bone cement 955 or other liquids. The
bone cement 955 can freely extravasate into the adjacent bone and marrow
space from several openings at the undersurface of the mini-prosthesis
960 thereby anchoring the mini-prosthesis.

[0043]FIG. 10A to C, are schematics depicting other exemplary knee
resurfacing devices and methods. FIG. 10A is a schematic depicting normal
thickness cartilage in the anterior and central and posterior portion of
a femoral condyle 1000 and a large area of diseased cartilage 1005 in the
posterior portion of the femoral condyle. FIG. 10B depicts placement of a
single component articular surface repair system 1010. The implantation
site has been prepared with a single cut. The articular surface repair
system is not perpendicular to the adjacent normal cartilage 1000. FIG.
10C depicts a multi-component articular surface repair system 1020. The
implantation site has been prepared with a single cut. The deep component
1030 has a curvature similar to that of the adjacent subchondral bone
1035. The superficial component 1040 has a curvature similar to that of
the adjacent cartilage 1000.

[0044]FIG. 11A and B show exemplary single and multiple component devices.
FIG. 11A shows an exemplary a single component articular surface repair
system 1100 with varying curvature and radii. In this case, the articular
surface repair system is chosen to include convex and concave portions.
Such devices can be preferable in a lateral femoral condyle or small
joints such as the elbow joint. FIG. 11B depicts a multi-component
articular surface repair system with a deep component 1110 that mirrors
the shape of the subchondral bone and a superficial component 1105
closely matching the shape and curvature of the surrounding normal
cartilage 1115. The deep component 1110 and the superficial component
1105 demonstrate varying curvatures and radii with convex and concave
portions.

[0045]FIGS. 12A and B show exemplary articular repair systems 100 having
an outer contour matching the surrounding normal cartilage 200. The
systems are implanted into the underlying bone 300 using one or more pegs
150, 175. The pegs may be porous-coated and may have flanges 125 as shown
in FIG. 12B.

[0046]FIG. 13 shows an example of a surgical tool 410 having one surface
400 matching the geometry of an articular surface of the joint. Also
shown is an aperture 415 in the tool 410 capable of controlling drill
depth and width of the hole and allowing implantation of an insertion of
implant 420 having a press-fit design.

[0047]FIG. 14 shows an exemplary articular repair device 500 including a
flat surface 510 to control depth and prevent toggle; an exterior surface
515 having the contour of normal cartilage; flanges 517 to prevent
rotation and control toggle; a groove 520 to facilitate tissue in-growth.

[0048]FIG. 15 depicts, in cross-section, an example of a surgical tool 600
containing apertures 605 through which a surgical drill or saw can fit
and which guide the drill or saw to make cuts or holes in the bone 610.
Dotted lines represent where the cuts corresponding to the apertures will
be made in bone.

[0049]FIG. 16 depicts, in cross-section, another example of a surgical
tool 620 containing an aperture 625 through which a surgical drill or saw
can fit. The aperture guides the drill or saw to make the proper hole or
cut in the underlying bone 630. Dotted lines represent where the cut
corresponding to the aperture will be made in bone.

[0050]FIG. 17A-D depict, in cross-section, another example of an implant
640 with multiple anchoring pegs 645. FIGS. 17B-D show various
cross-sectional representations of the pegs: FIG. 17B shows a peg having
a groove; FIG. 17C shows a peg with radially-extending arms that help
anchor the device in the underlying bone; and FIG. 17D shows a peg with
multiple grooves or flanges.

[0051]FIGS. 18A and B depict an overhead view of an exemplary implant 650
with multiple anchoring pegs 655 and depict how the pegs are not
necessarily linearly aligned along the longitudinal axis of the device.

[0052]FIG. 19A-E depict an exemplary implant 660 having radially extending
arms 665. FIG. 19B-E are overhead views of the implant showing that the
shape of the peg need not be conical.

DETAILED DESCRIPTION OF THE INVENTION

[0053]The current invention provides for methods and devices for
integration of cartilage replacement or regenerating materials.

[0054]Before describing the present invention in detail, it is to be
understood that this invention is not limited to particular formulations
or process parameters as such may, of course, vary. It is also to be
understood that the terminology used herein is for the purpose of
describing particular embodiments of the invention only, and is not
intended to be limiting.

[0056]All publications, patents and patent applications cited herein,
whether above or below, are hereby incorporated by reference in their
entirety.

[0057]It must be noted that, as used in this specification and the
appended claims, the singular forms "a", "an", and "the" include plural
references unless the content clearly dictates otherwise. Thus, for
example, reference to "an implantation site" includes a one or more such
sites.

DEFINITIONS

[0058]Unless defined otherwise, all technical and scientific terms used
herein have the same meaning as commonly understood by one of ordinary
skill in the art to which the invention pertains. Although any methods
and materials similar or equivalent to those described herein can be used
in the practice for testing of the present invention, the preferred
materials and methods are described herein.

[0059]The term "arthritis" refers to a group of conditions characterized
by progressive deterioration of joints. Thus, the term encompasses a
group of different diseases including, but not limited to, osteoarthritis
(OA), rheumatoid arthritis, seronegative spondyloarthropathies and
posttraumatic joint deformity.

[0060]The term "articular" refers to any joint. Thus, "articular
cartilage" refers to cartilage in a joint such as a knee, ankle, hip,
etc. The term "articular surface" refers to a surface of an articulating
bone that is covered by cartilage. For example, in a knee joint several
different articular surfaces are present, e.g. in the patella, the medial
femoral condyle, the lateral femoral condyle, the medial tibial plateau
and the lateral tibial plateau.

[0061]The term "weight-bearing surface" refers to the contact area between
two opposing articular surfaces during activities of normal daily living,
e.g., normal gait. The weight-bearing surface can be determined by any
suitable means, for example based on data published in the literature,
e.g. anatomic studies. The weight-bearing surface can be determined by
superimposing predetermined angles of flexion, extension, translation,
tilting and rotation on anatomic models, e.g. of the femur and the tibia.
Anatomic models can be generated with use of an imaging test. Biomotion
analysis, for example using optoelectronic registration means (see also
International Publication WO 02/22014) can also be used to define the
weight-bearing surface. Moreover, kinematic imaging tests such as
fluoroscopy or MRI of joint motion can be used to estimate the
weight-bearing surface for different physical activities. Different
modalities for determining the weight-bearing area such as 2D x-ray
fluoroscopy and MRI can be merged in order to estimate the weight-bearing
area. The weight-bearing area can be determined using any current and
future optical, electronic, imaging, or other means of assessing joint
motion.

[0062]The term "cartilage" or "cartilage tissue" as used herein is
generally recognized in the art, and refers to a specialized type of
dense connective tissue comprising cells embedded in an extracellular
matrix (ECM) (see, for example, Cormack, 1987, Ham's Histology, 9th Ed.,
J. B. Lippincott Co., pp. 266-272). The biochemical composition of
cartilage differs according to type. Several types of cartilage are
recognized in the art, including, for example, hyaline cartilage such as
that found within the joints, fibrous cartilage such as that found within
the meniscus and costal regions, and elastic cartilage. Hyaline
cartilage, for example, comprises chondrocytes surrounded by a dense ECM
consisting of collagen, proteoglycans and water. Fibrocartilage can form
in areas of hyaline cartilage, for example after an injury or, more
typically, after certain types of surgery. The production of any type of
cartilage is intended to fall within the scope of the invention.

[0063]Furthermore, although described primarily in relation to methods for
use in humans, the invention may also be practiced so as repair cartilage
tissue in any mammal in need thereof, including horses, dogs, cats,
sheep, pigs, among others. The treatment of such animals is intended to
fall within the scope of the invention.

[0064]The terms "articular repair system" and "articular surface repair
system" include any system (including, for example, compositions, devices
and techniques) to repair, to replace or to regenerate a portion of a
joint or an entire joint. The term encompasses systems that repair
articular cartilage, articular bone or both bone and cartilage. Articular
surface repair systems may also include a meniscal repair system (e.g.,
meniscal repair system can be composed of a biologic or non-biologic
material), for example a meniscal repair system having biomechanical
and/or biochemical properties similar to that of healthy menisci. See,
for example, U.S. Pat. Publication No. b 2002/0,022,884A1. The meniscal
repair system can be surgically or arthroscopically attached to the joint
capsule or one or more ligaments. Non-limiting examples of repair systems
include metal or plastic implants, polymer implants, combinations
thereof, injectable repair materials, for example materials that are
self-hardening, autologous chondrocyte transplantation, osteochondral
allografting, osteochondral autografting, tibial corticotomy, femoral
and/or tibial osteotomy. Repair systems also include treatment with
cartilage or bone tissue grown ex vivo as well as in vivo, stem cells,
cartilage material grown with use of stem cells, fetal cells or immature
or mature cartilage cells, an artificial non-human material, an agent
that stimulates repair of diseased cartilage tissue, an agent that
stimulates growth of cells, an agent that protects diseased cartilage
tissue and that protects adjacent normal cartilage tissue. Articular
repair systems include also treatment with a cartilage tissue transplant,
a cartilage tissue graft, a cartilage tissue implant, a cartilage tissue
scaffold, or any other cartilage tissue replacement or regenerating
material. Articular repair systems may include also treatment with a bone
tissue transplant, a bone tissue graft, a bone tissue implant, a bone
tissue scaffold, or any other bone tissue replacement or regenerating
material. Articular repair systems may also include treatment with a
meniscus tissue transplant, a meniscus tissue graft, a meniscus tissue
implant, a meniscus tissue scaffold, or any other meniscus tissue
replacement or regenerating material. Articular repair systems include
also surgical tools that facilitate the surgical procedure required for
articular repair, for example tools that prepare the area of diseased
cartilage tissue and/or subchondral bone for receiving, for example, a
cartilage tissue replacement or regenerating material. The term
"non-pliable" refers to material that cannot be significantly bent but
may retain elasticity.

[0065]The terms "replacement material" or "regenerating material" include
a broad range of natural and/or synthetic materials including metals,
metal alloys, polymers, injectables, combinations thereof used in the
methods described herein, for example, cartilage or bone tissue grown ex
vivo or in vivo, stem cells, cartilage material grown from stem cells,
stem cells, fetal cell, immature or mature cartilage cells, an agent that
stimulates growth of cells, an artificial non-human material, a tissue
transplant, a tissue graft, a tissue implant, a tissue scaffold, or a
tissue regenerating material. The term includes biological materials
isolated from various sources (e.g., cells) as well as modified (e.g.,
genetically modified) materials and/or combinations of isolated and
modified materials.

[0066]The term "imaging test" includes, but is not limited to, x-ray based
techniques (such as conventional film based x-ray films, digital x-ray
images, single and dual x-ray absorptiometry, radiographic
absorptiometry); fluoroscopic imaging, for example with C-arm devices
including C-arm devices with tomographic or cross-sectional imaging
capability, digital x-ray tomosynthesis, x-ray imaging including digital
x-ray tomosynthesis with use of x-ray contrast agents, for example after
intra-articular injection, ultrasound including broadband ultrasound
attenuation measurement and speed of sound measurements, A-scan, B-scan
and C-scan; computed tomography; nuclear scintigraphy; SPECT; positron
emission tomography, optical coherence tomography and MRI. One or more of
these imaging tests may be used in the methods described herein, for
example in order to obtain certain morphological information about one or
several tissues such as bone including bone mineral density and curvature
of the subchondral bone, cartilage including biochemical composition of
cartilage, cartilage thickness, cartilage volume, cartilage curvature,
size of an area of diseased cartilage, severity of cartilage disease or
cartilage loss, marrow including marrow composition, synovium including
synovial inflammation, lean and fatty tissue, and thickness, dimensions
and volume of soft and hard tissues. The imaging test can be performed
with use of a contrast agent, such as Gd-DTPA in the case of MRI.

[0067]The term "A-scan" refers to an ultrasonic technique where an
ultrasonic source transmits an ultrasonic wave into an object, such as
patient's body, and the amplitude of the returning echoes (signals) are
recorded as a function of time. Only structures that lie along the
direction of propagation are interrogated. As echoes return from
interfaces within the object or tissue, the transducer crystal produces a
voltage that is proportional to the echo intensity. The sequence of
signal acquisition and processing of the A-scan data in a modern
ultrasonic instrument usually occurs in six major steps:

[0068](1) Detection of the echo (signal) occurs via mechanical deformation
of the piezoelectric crystal and is converted to an electric signal
having a small voltage.

[0069](2) Preamplification of the electronic signal from the crystal, into
a more useful range of voltages is usually necessary to ensure
appropriate signal processing.

[0070](3) Time Gain Compensation compensates for the attenuation of the
ultrasonic signal with time, which arises from travel distance. Time gain
compensation may be user-adjustable and may be changed to meet the needs
of the specific application. Usually, the ideal time gain compensation
curve corrects the signal for the depth of the reflective boundary. Time
gain compensation works by increasing the amplification factor of the
signal as a function of time after the ultrasonic pulse has been emitted.
Thus, reflective boundaries having equal abilities to reflect ultrasonic
waves will have equal ultrasonic signals, regardless of the depth of the
boundary.

[0071](4) Compression of the time compensated signal can be accomplished
using logarithmic amplification to reduce the large dynamic range (range
of smallest to largest signals) of the echo amplitudes. Small signals are
made larger and large signals are made smaller. This step provides a
convenient scale for display of the amplitude variations on the limited
gray scale range of a monitor.

[0072](5) Rectification, demodulation and envelope detection of the high
frequency electronic signal permits the sampling and digitization of the
echo amplitude free of variations induced by the sinusoidal nature of the
waveform.

[0074]The term "B-scan" refers to an ultrasonic technique where the
amplitude of the detected returning echo is recorded as a function of the
transmission time, the relative location of the detector in the probe and
the signal amplitude. This is often represented by the brightness of a
visual element, such as a pixel, in a two-dimensional image. The position
of the pixel along the y-axis represents the depth, i.e. half the time
for the echo to return to the transducer (for one half of the distance
traveled). The position along the x-axis represents the location of the
returning echoes relative to the long axis of the transducer, i.e. the
location of the pixel either in a superoinferior or mediolateral
direction or a combination of both. The display of multiple adjacent scan
lines creates a composite two-dimensional image that portrays the general
contour of internal organs.

[0075]The term "C-scan" refers to an ultrasonic technique where additional
gating electronics are incorporated into a B-scan to eliminate
interference from underlying or overlying structures by scanning at a
constant-depth. An interface reflects part of the ultrasonic beam energy.
All interfaces along the scan line may contribute to the measurement. The
gating electronics of the C-mode rejects all returning echoes except
those received during a specified time interval. Thus, only scan data
obtained from a specific depth range are recorded. Induced signals
outside the allowed period are not amplified and, thus, are not processed
and displayed. C-mode-like methods are also described herein for A-scan
techniques and devices in order to reduce the probe/skin interface
reflection. The term "repair" is used in a broad sense to refer to one or
more repairs to damaged joints (e.g., cartilage or bone) or to
replacement of one or more components or regions of the joint. Thus, the
term encompasses both repair (e.g., one or more portions of a cartilage
and/or layers of cartilage or bone) and replacement (e.g., of an entire
cartilage).

[0076]The term "C-arm" refers to a fluoroscopic x-ray system mounted on a
C-shaped arch that allows it to rotate and/or tilt passively or actively
around the object to be imaged. The x-ray beam that is transmitted by the
x-ray source through the object and received by the detector is displayed
on a screen. C-arm typically includes systems that have cross-sectional
imaging capability, for example by using rotation of the x-ray tube and
detector to reconstruct a cross-sectional image similar to a CT rather
than a conventional projectional x-ray only.

[0077]The terms "hardening," "solidifying," and "curable" refers to any
liquid or sufficiently flowable material that forms a solid or gel,
either over time, upon contact with another substance and/or upon
application of energy.

[0078]General Overview

[0079]The present invention provides methods and compositions for
repairing joints, particularly for repairing articular cartilage and for
facilitating the integration of a wide variety of cartilage repair
materials into a subject. Among other things, the techniques described
herein allow for the customization of cartilage repair material to suit a
particular subject, for example in terms of size, cartilage thickness
and/or curvature. When the shape (e.g., size, thickness and/or curvature)
of the articular cartilage surface is an exact or near anatomic fit with
the non-damaged cartilage or with the subject's original cartilage, the
success of repair is enhanced. The repair material may be shaped prior to
implantation and such shaping can be based, for example, on electronic
images that provide information regarding curvature or thickness of any
"normal" cartilage surrounding the defect and/or on curvature of the bone
underlying the defect. Thus, the current invention provides, among other
things, for minimally invasive methods for partial joint replacement. The
methods will require only minimal or, in some instances, no loss in bone
stock. Additionally, unlike with current techniques, the methods
described herein will help to restore the integrity of the articular
surface by achieving an exact or near anatomic match between the implant
and the surrounding or adjacent cartilage and/or subchondral bone.

[0080]Advantages of the present invention can include, but are not limited
to, (i) customization of joint repair, thereby enhancing the efficacy and
comfort level for the patient following the repair procedure; (ii)
eliminating the need for a surgeon to measure the defect to be repaired
intraoperatively in some embodiments; (iii) eliminating the need for a
surgeon to shape the material during the implantation procedure; (iv)
providing methods of evaluating curvature of the repair material based on
bone or tissue images or based on intraoperative probing techniques; (v)
providing methods of repairing joints with only minimal or, in some
instances, no loss in bone stock; and (vi) improving postoperative joint
congruity.

[0081]Thus, the methods described herein allow for the design and use of
joint repair material that more precisely fits the defect (e.g., site of
implantation) and, accordingly, provides improved repair of the joint.

[0082]1.0. Assessment of Defects

[0083]The methods and compositions described herein may be used to treat
defects resulting from disease of the cartilage (e.g., osteoarthritis),
bone damage, cartilage damage, trauma, and/or degeneration due to overuse
or age. The invention allows, among other things, a health practitioner
to evaluate and treat such defects. The size, volume and shape of the
area of interest may include only the region of cartilage that has the
defect, but preferably will also include contiguous parts of the
cartilage surrounding the cartilage defect.

[0084]Size, curvature and/or thickness measurements can be obtained using
any suitable techniques, for example in one direction, two directions,
and/or in three dimensions for example, using suitable mechanical means,
laser devices, molds, materials applied to the articular surface that
harden and "memorize the surface contour," and/or one or more imaging
techniques. Measurements may be obtained non-invasively and/or
intraoperatively (e.g., using a probe or other surgical device).

[0087]In certain embodiments, CT or MRI is used to assess tissue, bone,
cartilage and any defects therein, for example cartilage lesions or areas
of diseased cartilage, to obtain information on subchondral bone or
cartilage degeneration and to provide morphologic or biochemical or
biomechanical information about the area of damage. Specifically, changes
such as fissuring, partial or full thickness cartilage loss, and signal
changes within residual cartilage can be detected using one or more of
these methods. For discussions of the basic NMR principles and
techniques, see MRI Basic Principles and Applications, Second Edition,
Mark A. Brown and Richard C. Semelka, Wiley-Liss, Inc. (1999). For a
discussion of MRI including conventional T1 and T2-weighted spin-echo
imaging, gradient recalled echo (GRE) imaging, magnetization transfer
contrast (MTC) imaging, fast spin-echo (FSE) imaging, contrast enhanced
imaging, rapid acquisition relaxation enhancement, (RARE) imaging,
gradient echo acquisition in the steady state, (GRASS), and driven
equilibrium Fourier transform (DEFT) imaging, to obtain information on
cartilage, see WO 02/22014. Thus, in preferred embodiments, the
measurements are three-dimensional images obtained as described in WO
02/22014. Three-dimensional internal images, or maps, of the cartilage
alone or in combination with a movement pattern of the joint can be
obtained. Three-dimensional internal images can include information on
biochemical composition of the articular cartilage. In addition, imaging
techniques can be compared over time, for example to provide up to date
information on the shape and type of repair material needed.

[0088]Any of the imaging devices described herein may also be used
intra-operatively (see, also below), for example using a hand-held
ultrasound and/or optical probe to image the articular surface
intra-operatively.

[0089]1.2. Intra-Operative Measurements

[0090]Alternatively, or in addition to, non-invasive imaging techniques,
measurements of the size of an area of diseased cartilage or an area of
cartilage loss, measurements of cartilage thickness and/or curvature of
cartilage or bone can be obtained intraoperatively during arthroscopy or
open arthrotomy. Intraoperative measurements may or may not involve
actual contact with one or more areas of the articular surfaces.

[0091]Devices to obtain intraoperative measurements of cartilage, and to
generate a topographical map of the surface include but are not limited
to, Placido disks and laser interferometers, and/or deformable materials.
(See, for example, U.S. Pat. Nos. 6,382,028; 6,057,927; 5,523,843;
5,847,804; and 5,684,562). For example, a Placido disk (a concentric
array that projects well-defined circles of light of varying radii,
generated either with laser or white light transported via optical fiber)
can be attached to the end of an endoscopic device (or to any probe, for
example a hand-held probe) so that the circles of light are projected
onto the cartilage surface. One or more imaging cameras can be used
(e.g., attached to the device) to capture the reflection of the circles.
Mathematical analysis is used to determine the surface curvature. The
curvature can then be visualized on a monitor as a color-coded,
topographical map of the cartilage surface. Additionally, a mathematical
model of the topographical map can be used to determine the ideal surface
topography to replace any cartilage defects in the area analyzed. This
computed, ideal surface can then also be visualized on the monitor, and
is used to select the curvature of the replacement material or
regenerating material.

[0092]Similarly a laser interferometer can also be attached to the end of
an endoscopic device. In addition, a small sensor may be attached to the
device in order to determine the cartilage surface curvature using phase
shift interferometry, producing a fringe pattern analysis phase map (wave
front) visualization of the cartilage surface. The curvature can then be
visualized on a monitor as a color coded, topographical map of the
cartilage surface. Additionally, a mathematical model of the
topographical map can be used to determine the ideal surface topography
to replace any cartilage defects in the area analyzed. This computed,
ideal surface can then also be visualized on the monitor, and can be used
to select the curvature of the replacement cartilage.

[0093]One skilled in the art will readily recognize other techniques for
optical measurements of the cartilage surface curvature.

[0094]Mechanical devices (e.g., probes) may also be used for
intraoperative measurements, for example, deformable materials such as
gels, molds, any hardening materials (e.g., materials that remain
deformable until they are heated, cooled, or otherwise manipulated). See,
e.g., WO 02/34310. For example, a deformable gel can be applied to a
femoral condyle. The side of the gel pointing towards the condyle will
yield a negative impression of the surface contour of the condyle. Said
negative impression can be used to determine the size of a defect, the
depth of a defect and the curvature of the articular surface in and
adjacent to a defect. This information can be used to select a therapy,
e.g. an articular surface repair system. In another example, a hardening
material can be applied to an articular surface, e.g. a femoral condyle
or a tibial plateau. Said hardening material will remain on the articular
surface until hardening has occurred. The hardening material will then be
removed from the articular surface. The side of the hardening material
pointing towards the articular surface will yield a negative impression
of the articular surface. The negative impression can be used to
determine the size of a defect, the depth of a defect and the curvature
of the articular surface in and adjacent to a defect. This information
can be used to select a therapy, e.g. an articular surface repair system.

[0095]In certain embodiments, the deformable material comprises a
plurality of individually moveable mechanical elements. When pressed
against the surface of interest, each element may be pushed in the
opposing direction and the extent to which it is pushed (deformed) will
correspond to the curvature of the surface of interest. The device may
include a brake mechanism so that the elements are maintained in the
position that mirrors the surface of the cartilage and/or bone. The
device can then be removed from the patient and analyzed for curvature.
Alternatively, each individual moveable element may include markers
indicating the amount and/or degree they are deformed at a given spot. A
camera can be used to intra-operatively image the device and the image
can be saved and analyzed for curvature information. Suitable markers
include, but are not limited to, actual linear measurements (metric or
imperial), different colors corresponding to different amounts of
deformation and/or different shades or hues of the same color(s).

[0096]Other devices to measure cartilage and subchondral bone
intraoperatively include, for example, ultrasound probes. An ultrasound
probe, preferably handheld, can be applied to the cartilage and the
curvature of the cartilage and/or the subchondral bone can be measured.
Moreover, the size of a cartilage defect can be assessed and the
thickness of the articular cartilage can be determined. Such ultrasound
measurements can be obtained in A-mode, B-mode, or C-mode. If A-mode
measurements are obtained, an operator will typically repeat the
measurements with several different probe orientations, e.g. mediolateral
and anteroposterior, in order to derive a three-dimensional assessment of
size, curvature and thickness.

[0097]One skilled in the art will easily recognize that different probe
designs are possible using said optical, laser interferometry, mechanical
and ultrasound probes. The probes are preferably handheld. In certain
embodiments, the probes or at least a portion of the probe, typically the
portion that is in contact with the tissue, will be sterile. Sterility
can be achieved with use of sterile covers, for example similar to those
disclosed in WO9908598A1.

[0098]Analysis on the curvature of the articular cartilage or subchondral
bone using imaging tests and/or intraoperative measurements can be used
to determine the size of an area of diseased cartilage or cartilage loss.
For example, the curvature can change abruptly in areas of cartilage
loss. Such abrupt or sudden changes in curvature can be used to detect
the boundaries of diseased cartilage or cartilage defects.

[0099]1.3. Models

[0100]Using information on thickness and curvature of the cartilage, a
physical model of the surfaces of the articular cartilage and of the
underlying bone can be created. This physical model can be representative
of a limited area within the joint or it can encompass the entire joint.
For example, in the knee joint, the physical model can encompass only the
medial or lateral femoral condyle, both femoral condyles and the notch
region, the medial tibial plateau, the lateral tibial plateau, the entire
tibial plateau, the medial patella, the lateral patella, the entire
patella or the entire joint. The location of a diseased area of cartilage
can be determined, for example using a 3D coordinate system or a 3D
Euclidian distance as described in WO 02/22014.

[0101]In this way, the size of the defect to be repaired can be
determined. As will be apparent, some, but not all, defects will include
less than the entire cartilage. Thus, in one embodiment of the invention,
the thickness of the normal or only mildly diseased cartilage surrounding
one or more cartilage defects is measured. This thickness measurement can
be obtained at a single point or, preferably, at multiple points, for
example 2 point, 4-6 points, 7-10 points, more than 10 points or over the
length of the entire remaining cartilage. Furthermore, once the size of
the defect is determined, an appropriate therapy (e.g., articular repair
system) can be selected such that as much as possible of the healthy,
surrounding tissue is preserved.

[0102]In other embodiments, the curvature of the articular surface can be
measured to design and/or shape the repair material. Further, both the
thickness of the remaining cartilage and the curvature of the articular
surface can be measured to design and/or shape the repair material.
Alternatively, the curvature of the subchondral bone can be measured and
the resultant measurement(s) can be used to either select or shape a
cartilage replacement material.

[0103]2.0. Repair Materials

[0104]A wide variety of materials find use in the practice of the present
invention, including, but not limited to, plastics, metals, ceramics,
biological materials (e.g., collagen or other extracellular matrix
materials), hydroxyapatite, cells (e.g., stem cells, chondrocyte cells or
the like), or combinations thereof. Based on the information (e.g.,
measurements) obtained regarding the defect and the articular surface
and/or the subchondral bone, a repair material can be formed or selected.
Further, using one or more of these techniques described herein, a
cartilage replacement or regenerating material having a curvature that
will fit into a particular cartilage defect, will follow the contour and
shape of the articular surface, and will match the thickness of the
surrounding cartilage. The repair material may include any combination of
materials, and preferably includes at least one non-pliable (hard)
material.

[0105]2.1. Metal and Polymeric Repair Materials

[0106]Currently, joint repair systems often employ metal and/or polymeric
materials including, for example, prosthesis which are anchored into the
underlying bone (e.g., a femur in the case of a knee prosthesis). See,
e.g., U.S. Pat. Nos. 6,203,576 and 6,322,588 and references cited
therein. A wide-variety of metals may find use in the practice of the
present invention, and may be selected based on any criteria, for
example, based on resiliency to impart a desired degree of rigidity.
Non-limiting examples of suitable metals include silver, gold, platinum,
palladium, iridium, copper, tin, lead, antimony, bismuth, zinc, titanium,
cobalt, stainless steel, nickel, iron alloys, cobalt alloys, such as
Elgiloy®, a cobalt-chromium-nickel alloy, and MP35N, a
nickel-cobalt-chromium-molybdenum alloy, and Nitinol®, a
nickel-titanium alloy, aluminum, manganese, iron, tantalum, other metals
that can slowly form polyvalent metal ions, for example to inhibit
calcification of implanted substrates in contact with a patient's bodily
fluids or tissues, and combinations thereof.

[0108]The polymers can be prepared by any of a variety of approaches
including conventional polymer processing methods. Preferred approaches
include, for example, injection molding, which is suitable for the
production of polymer components with significant structural features,
and rapid prototyping approaches, such as reaction injection molding and
stereo-lithography. The substrate can be textured or made porous by
either physical abrasion or chemical alteration to facilitate
incorporation of the metal coating.

[0109]More than one metal and/or polymer may be used in combination with
each other. For example, one or more metal-containing substrates may be
coated with polymers in one or more regions or, alternatively, one or
more polymer-containing substrate may be coated in one or more regions
with one or more metals.

[0110]The system or prosthesis can be porous or porous coated. The porous
surface components can be made of various materials including metals,
ceramics, and polymers. These surface components can, in turn, be secured
by various means to a multitude of structural cores formed of various
metals. Suitable porous coatings include, but are not limited to, metal,
ceramic, polymeric (e.g., biologically neutral elastomers such as
silicone rubber, polyethylene terephthalate and/or combinations thereof)
or combinations thereof. See, e.g., Hahn U.S. Pat. No. 3,605,123. Tronzo
U.S. Pat. No. 3,808,606 and Tronzo U.S. Pat. No. 3,843,975; Smith U.S.
Pat. No. 3,314,420; Scharbach U.S. Pat. No. 3,987,499; and German
Offenlegungsschrift 2,306,552. There may be more than one coating layer
and the layers may have the same or different porosities. See, e.g., U.S.
Pat. No. 3,938,198.

[0111]The coating may be applied by surrounding a core with powdered
polymer and heating until cured to form a coating with an internal
network of interconnected pores. The tortuosity of the pores (e.g., a
measure of length to diameter of the paths through the pores) may be
important in evaluating the probable success of such a coating in use on
a prosthetic device. See, also, Morris U.S. Pat. No. 4,213,816. The
porous coating may be applied in the form of a powder and the article as
a whole subjected to an elevated temperature that bonds the powder to the
substrate. Selection of suitable polymers and/or powder coatings may be
determined in view of the teachings and references cited herein, for
example based on the melt index of each.

[0112]2.2. Biological Repair Materials

[0113]Repair materials may also include one or more biological material
either alone or in combination with non-biological materials. For
example, any base material can be designed or shaped and suitable
cartilage replacement or regenerating material(s) such as fetal cartilage
cells can be applied to be the base. The cells can be then be grown in
conjunction with the base until the thickness (and/or curvature) of the
cartilage surrounding the cartilage defect has been reached. Conditions
for growing cells (e.g., chondrocytes) on various substrates in culture,
ex vivo and in vivo are described, for example, in U.S. Pat. Nos.
5,478,739; 5,842,477; 6,283,980 and 6,365,405. Non-limiting examples of
suitable substrates include plastic, tissue scaffold, a bone replacement
material (e.g., a hydroxyapatite, a bioresorbable material), or any other
material suitable for growing a cartilage replacement or regenerating
material on it.

[0115]Biological materials used in the methods described herein can be
autografts (from the same subject); allografts (from another individual
of the same species) and/or xenografts (from another species). See, also,
International Patent Publications WO 02/22014 and WO 97/27885. In certain
embodiments autologous materials are preferred, as they may carry a
reduced risk of immunological complications to the host, including
re-absorption of the materials, inflammation and/or scarring of the
tissues surrounding the implant site.

[0116]In one embodiment of the invention, a probe is used to harvest
tissue from a donor site and to prepare a recipient site. The donor site
can be located in a xenograft, an allograft or an autograft. The probe is
used to achieve a good anatomic match between the donor tissue sample and
the recipient site. The probe is specifically designed to achieve a
seamless or near seamless match between the donor tissue sample and the
recipient site. The probe can, for example, be cylindrical. The distal
end of the probe is typically sharp in order to facilitate tissue
penetration. Additionally, the distal end of the probe is typically
hollow in order to accept the tissue. The probe can have an edge at a
defined distance from its distal end, e.g. at 1 cm distance from the
distal end and the edge can be used to achieve a defined depth of tissue
penetration for harvesting. The edge can be external or can be inside the
hollow portion of the probe. For example, an orthopedic surgeon can take
the probe and advance it with physical pressure into the cartilage, the
subchondral bone and the underlying marrow in the case of a joint such as
a knee joint. The surgeon can advance the probe until the external or
internal edge reaches the cartilage surface. At that point, the edge will
prevent further tissue penetration thereby achieving a constant and
reproducible tissue penetration. The distal end of the probe can include
a blade or saw-like structure or tissue cutting mechanism. For example,
the distal end of the probe can include an iris-like mechanism consisting
of several small blades. The at least one or more blades can be moved
using a manual, motorized or electrical mechanism thereby cutting through
the tissue and separating the tissue sample from the underlying tissue.
Typically, this will be repeated in the donor and the recipient. In the
case of an iris-shaped blade mechanism, the individual blades can be
moved so as to close the iris thereby separating the tissue sample from
the donor site.

[0117]In another embodiment of the invention, a laser device or a
radiofrequency device can be integrated inside the distal end of the
probe. The laser device or the radiofrequency device can be used to cut
through the tissue and to separate the tissue sample from the underlying
tissue.

[0118]In one embodiment of the invention, the same probe can be used in
the donor and in the recipient. In another embodiment, similarly shaped
probes of slightly different physical dimensions can be used. For
example, the probe used in the recipient can be slightly smaller than
that used in the donor thereby achieving a tight fit between the tissue
sample or tissue transplant and the recipient site. The probe used in the
recipient can also be slightly shorter than that used in the donor
thereby correcting for any tissue lost during the separation or cutting
of the tissue sample from the underlying tissue in the donor material.

[0119]Any biological repair material may be sterilized to inactivate
biological contaminants such as bacteria, viruses, yeasts, molds,
mycoplasmas and parasites. Sterilization may be performed using any
suitable technique, for example radiation, such as gamma radiation.

[0120]Any of the biological material described herein may be harvested
with use of a robotic device. The robotic device can use information from
an electronic image for tissue harvesting.

[0121]In certain embodiments, the cartilage replacement material has a
particular biochemical composition. For instance, the biochemical
composition of the cartilage surrounding a defect can be assessed by
taking tissue samples and chemical analysis or by imaging techniques. For
example, WO 02/22014 describes the use of gadolinium for imaging of
articular cartilage to monitor glycosaminoglycan content within the
cartilage. The cartilage replacement or regenerating material can then be
made or cultured in a manner, to achieve a biochemical composition
similar to that of the cartilage surrounding the implantation site. The
culture conditions used to achieve the desired biochemical compositions
can include, for example, varying concentrations biochemical composition
of said cartilage replacement or regenerating material can, for example,
be influenced by controlling concentrations and exposure times of certain
nutrients and growth factors.

[0122]2.3. Multiple-Component Repair Materials

[0123]The articular repair system may include one or more components.
Non-limiting examples of one-component systems include a plastic, a
polymer, a metal, a metal alloy, a biologic material or combinations
thereof. In certain embodiments, the surface of the repair system facing
the underlying bone is smooth. In other embodiments, the surface of the
repair system facing the underlying bone is porous or porous-coated. In
another aspect, the surface of the repair system facing the underlying
bone is designed with one or more grooves, for example to facilitate the
in-growth of the surrounding tissue. The external surface of the device
can have a step-like design, which can be advantageous for altering
biomechanical stresses. Optionally, flanges can also be added at one or
more positions on the device (e.g., to prevent the repair system from
rotating, to control toggle and/or prevent settling into the marrow
cavity). The flanges can be part of a conical or a cylindrical design. A
portion or all of the repair system facing the underlying bone can also
be flat which may help to control depth of the implant and to prevent
toggle. (See, also FIGS. 12, 13 and 14).

[0124]Non-limiting examples of multiple-component systems include
combinations of metal, plastic, metal alloys and one or more biological
materials. One or more components of the articular surface repair system
can be composed of a biologic material (e.g. a tissue scaffold with cells
such as cartilage cells or stem cells alone or seeded within a substrate
such as a bioresorable material or a tissue scaffold, allograft,
autograft or combinations thereof) and/or a non-biological material
(e.g., polyethylene or a chromium alloy such as chromium cobalt).

[0125]Thus, the repair system can include one or more areas of a single
material or a combination of materials, for example, the articular
surface repair system can have a superficial and a deep component. The
superficial component is typically designed to have size, thickness and
curvature similar to that of the cartilage tissue lost while the deep
component is typically designed to have a curvature similar to the
subchondral bone. In addition, the superficial component can have
biomechanical properties similar to articular cartilage, including but
not limited to similar elasticity and resistance to axial loading or
shear forces. The superficial and the deep component can consist of two
different metals or metal alloys. One or more components of the system
(e.g., the deep portion) can be composed of a biologic material
including, but not limited to bone, or a non-biologic material including,
but not limited to hydroxyapatite, tantalum, a chromium alloy, chromium
cobalt or other metal alloys.

[0126]One or more regions of the articular surface repair system (e.g.,
the outer margin of the superficial portion and/or the deep portion) can
be bioresorbable, for example to allow the interface between the
articular surface repair system and the patient's normal cartilage, over
time, to be filled in with hyaline or fibrocartilage. Similarly, one or
more regions (e.g., the outer margin of the superficial portion of the
articular surface repair system and/or the deep portion) can be porous.
The degree of porosity can change throughout the porous region, linearly
or non-linearly, for where the degree of porosity will typically decrease
towards the center of the articular surface repair system. The pores can
be designed for in-growth of cartilage cells, cartilage matrix, and
connective tissue thereby achieving a smooth interface between the
articular surface repair system and the surrounding cartilage.

[0127]The repair system (e.g., the deep component in multiple component
systems) can be attached to the patient's bone with use of a cement-like
material such as methylmethacrylate, injectable hydroxy- or
calcium-apatite materials and the like.

[0128]In certain embodiments, one or more portions of the articular
surface repair system can be pliable or liquid or deformable at the time
of implantation and can harden later. Hardening can occur within 1 second
to 2 hours (or any time period therebetween), preferably with in 1 second
to 30 minutes (or any time period therebetween), more preferably between
1 second and 10 minutes (or any time period therebetween).

[0129]One or more components of the articular surface repair system can be
adapted to receive injections. For example, the external surface of the
articular surface repair system can have one or more openings therein.
The openings can be sized so as to receive screws, tubing, needles or
other devices which can be inserted and advanced to the desired depth,
for example through the articular surface repair system into the marrow
space. Injectables such as methylmethacrylate and injectable hydroxy- or
calcium-apatite materials can then be introduced through the opening (or
tubing inserted therethrough) into the marrow space thereby bonding the
articular surface repair system with the marrow space. Similarly, screws
or pins can be inserted into the openings and advanced to the underlying
subchondral bone and the bone marrow or epiphysis to achieve fixation of
the articular surface repair system to the bone. Portions or all
components of the screw or pin can be bioresorbable, for example, the
distal portion of a screw that protrudes into the marrow space can be
bioresorbable. During the initial period after the surgery, the screw can
provide the primary fixation of the articular surface repair system.
Subsequently, ingrowth of bone into a porous coated area along the
undersurface of the articular cartilage repair system can take over as
the primary stabilizer of the articular surface repair system against the
bone.

[0130]The articular surface repair system can be anchored to the patient's
bone with use of a pin or screw or other attachment mechanism. The
attachment mechanism can be bioresorbable. The screw or pin or attachment
mechanism can be inserted and advanced towards the articular surface
repair system from a non-cartilage covered portion of the bone or from a
non-weight-bearing surface of the joint.

[0131]The interface between the articular surface repair system and the
surrounding normal cartilage can be at an angle, for example oriented at
an angle of 90 degrees relative to the underlying subchondral bone.
Suitable angles can be determined in view of the teachings herein, and in
certain cases, non-90 degree angles may have advantages with regard to
load distribution along the interface between the articular surface
repair system and the surrounding normal cartilage.

[0132]The interface between the articular surface repair system and the
surrounding normal cartilage and/or bone may be covered with a
pharmaceutical or bioactive agent, for example a material that stimulates
the biological integration of the repair system into the normal cartilage
and/or bone. The surface area of the interface can be irregular, for
example, to increase exposure of the interface to pharmaceutical or
bioactive agents.

[0133]2.4. Customized Containers

[0134]In another embodiment of the invention, a container or well can be
formed to the selected specifications, for example to match the material
needed for a particular subject or to create a stock of repair materials
in a variety of sizes. The size and shape of the container may be
designed using the thickness and curvature information obtained from the
joint and from the cartilage defect. More specifically, the inside of the
container can be shaped to follow any selected measurements, for example
as obtained from the cartilage defect(s) of a particular subject. The
container can be filled with a cartilage replacement or regenerating
material, for example, collagen-containing materials, plastics,
bioresorbable materials and/or any suitable tissue scaffold. The
cartilage regenerating or replacement material can also consist of a
suspension of stem cells or fetal or immature or mature cartilage cells
that subsequently develop to more mature cartilage inside the container.
Further, development and/or differentiation can be enhanced with use of
certain tissue nutrients and growth factors.

[0135]The material is allowed to harden and/or grow inside the container
until the material has the desired traits, for example, thickness,
elasticity, hardness, biochemical composition, etc. Molds can be
generated using any suitable technique, for example computer devices and
automation, e.g. computer assisted design (CAD) and, for example,
computer assisted modeling (CAM). Because the resulting material
generally follows the contour of the inside of the container it will
better fit the defect itself and facilitate integration.

[0136]2.5. Shaping

[0137]In certain instances shaping of the repair material will be required
before or after formation (e.g., growth to desired thickness), for
example where the thickness of the required cartilage material is not
uniform (e.g., where different sections of the cartilage replacement or
regenerating material require different thicknesses).

[0138]The replacement material can be shaped by any suitable technique
including, but not limited to, mechanical abrasion, laser abrasion or
ablation, radiofrequency treatment, cryoablation, variations in exposure
time and concentration of nutrients, enzymes or growth factors and any
other means suitable for influencing or changing cartilage thickness.
See, e.g., WO 00/15153; If enzymatic digestion is used, certain sections
of the cartilage replacement or regenerating material can be exposed to
higher doses of the enzyme or can be exposed longer as a means of
achieving different thicknesses and curvatures of the cartilage
replacement or regenerating material in different sections of said
material.

[0139]The material can be shaped manually and/or automatically, for
example using a device into which a pre-selected thickness and/or
curvature has been inputted and programming the device to achieve the
desired shape.

[0140]In addition to, or instead of, shaping the cartilage repair
material, the site of implantation (e.g., bone surface, any cartilage
material remaining, etc.) can also be shaped by any suitable technique in
order to enhanced integration of the repair material.

[0141]2.6. Pre-Existing Repair Systems

[0142]As described herein, repair systems of various sizes, curvatures and
thicknesses can be obtained. These repair systems can be catalogued and
stored to create a library of systems from which an appropriate system
can then be selected. In other words, a defect is assessed in a
particular subject and a pre-existing repair system having the closest
shape and size is selected from the library for further manipulation
(e.g., shaping) and implantation.

[0143]2.7. Mini-Prosthesis

[0144]As noted above, the methods and compositions described herein can be
used to replace only a portion of the articular surface, for example, an
area of diseased cartilage or lost cartilage on the articular surface. In
these systems, the articular surface repair system may be designed to
replace only the area of diseased or lost cartilage or it can extend
beyond the area of diseased or lost cartilage, e.g., 3 or 5 mm into
normal adjacent cartilage. In certain embodiments, the prosthesis
replaces less than about 70% to 80% (or any value therebetween) of the
articular surface (e.g., any given articular surface such as a single
femoral condyle, etc.), preferably, less than about 50% to 70% (or any
value therebetween), more preferably, less than about 30% to 50% (or any
value therebetween), more preferably less than about 20% to 30% (or any
value therebetween), even more preferably less than about 20% of the
articular surface.

[0145]As noted above, the prosthesis may include multiple components, for
example a component that is implanted into the bone (e.g., a metallic
device) attached to a component that is shaped to cover the defect of the
cartilage overlaying the bone. Additional components, for example
intermediate plates, meniscus repairs systems and the like may also be
included. It is contemplated that each component replaces less than all
of the corresponding articular surface. However, each component need not
replace the same portion of the articular surface. In other words, the
prosthesis may have a bone-implanted component that replaces less than
30% of the bone and a cartilage component that replaces 60% of the
cartilage. The prosthesis may include any combination, so long as each
component replaces less than the entire articular surface.

[0146]The articular surface repair system may be formed or selected so
that it will achieve a near anatomic fit or match with the surrounding or
adjacent cartilage. Typically, the articular surface repair system is
formed and/or selected so that its outer margin located at the external
surface will be aligned with the surrounding or adjacent cartilage.

[0147]Thus, the articular repair system can be designed to replace the
weight-bearing portion (or more or less than the weight bearing portion)
of an articular surface, for example in a femoral condyle. The
weight-bearing surface refers to the contact area between two opposing
articular surfaces during activities of normal daily living (e.g., normal
gait). At least one or more weight-bearing portions can be replaced in
this manner, e.g., on a femoral condyle and on a tibia.

[0148]In other embodiments, an area of diseased cartilage or cartilage
loss can be identified in a weight-bearing area and only a portion of
said weight-bearing area, specifically the portion containing said
diseased cartilage or area of cartilage loss, can be replaced with an
articular surface repair system.

[0149]In another embodiment, for example in patients with diffuse
cartilage loss, the articular repair system can be designed to replace an
area slightly larger than the weight-bearing surface.

[0150]In certain aspects, the defect to be repaired is located only on one
articular surface, typically the most diseased surface. For example, in a
patient with severe cartilage loss in the medial femoral condyle but less
severe disease in the tibia, the articular surface repair system can only
be applied to the medial femoral condyle. Preferably, in any methods
described herein, the articular surface repair system is designed to
achieve an exact or a near anatomic fit with the adjacent normal
cartilage.

[0151]In other embodiments, more than one articular surface can be
repaired.

[0152]The area(s) of repair will be typically limited to areas of diseased
cartilage or cartilage loss or areas slightly greater than the area of
diseased cartilage or cartilage loss within the weight-bearing
surface(s).

[0153]The implant and/or the implant site can be sculpted to achieve a
near anatomic alignment between the implant and the implant site. In
another embodiment of the invention, an electronic image is used to
measure the thickness, curvature, or shape of the articular cartilage or
the subchondral bone, and/or the size of a defect, and an articular
surface repair system is selected using this information. The articular
surface repair system can be inserted arthroscopically. The articular
surface repair system can have a single radius. More typically, however,
the articular surface repair system 1100 can have varying curvatures and
radii within the same plane, e.g. anteroposterior or mediolateral or
superoinferior or oblique planes, or within multiple planes. In this
manner, the articular surface repair system can be shaped to achieve a
near anatomic alignment between the implant and the implant site. This
design allows not only allows for different degrees of convexity or
concavity, but also for concave portions within a predominantly convex
shape or vice versa 1100.

[0154]If a multiple component repair material has been selected, for
example with a superficial component 1105 consisting of a polymeric
material and a deep component 1110 consisting of a metal alloy, the
superficial component can be designed so that its thickness and curvature
will closely match that of the surrounding cartilage 1115. Thus, the
superficial component can have more than one thickness in different
portions of the articular repair system. Moreover, the superficial
component can have varying curvatures and radii within the same plane,
e.g. anteroposterior or mediolateral or superoinferior or oblique planes,
or within multiple planes. Similarly, the deep component can have varying
curvatures and radii within the same plane, e.g. anteroposterior or
mediolateral or superoinferior or oblique planes, or within multiple
planes. Typically, the curvature of the deep component will be designed
to follow that of the subchondral bone.

[0155]In another embodiment the articular surface repair system has a
fixturing stem, for example, as described in the Background of U.S. Pat.
No. 6,224,632. The fixturing stem can have different shapes including
conical, rectangular, fin among others. The mating bone cavity is
typically similarly shaped as the corresponding stem.

[0156]As shown in FIG. 12, the articular surface repair system 100 can be
affixed to the subchondral bone 300, with one or more fixturing stems
(pegs) 150 extending through the subchondral plate into the marrow space.
In certain instances, this design may reduce the likelihood that the
implant will settle deeper into the joint over time by resting portions
of the implant against the subchondral bone. The fixturing stems or pegs
can be of any shape, for example, cylindrical or conical. Optionally, the
fixturing stems or pegs can have notches or openings to allow bone
ingrowth. In addition, the fixturing stems or pegs can be porous coated
for bone ingrowth. The fixturing stems or pegs can be affixed to the bone
using bone cement. An anchoring device can be affixed to the fixturing
stem or peg. The anchoring device can have an umbrella shape (e.g.,
radially expanding elements) with the wider portion pointing towards the
subchondral bone and away from the peg. The anchoring device can be
advantageous for providing immediate fixation of the implant. The
undersurface of the articular repair system facing the subchondral bone
can be textured or rough thereby increasing the contact surface between
the articular repair system and the subchondral bone. Alternatively, the
undersurface of the articular repair system can be porous coated thereby
allowing ingrowth. The surgeon can support the ingrowth of bone by
treating the subchondral bone with a rasp, typically to create a larger
surface area and/or until bleeding from the subchondral bone occurs.

[0157]In another embodiment, the articular surface repair system can be
attached to the underlying bone or bone marrow using bone cement. Bone
cement is typically made from an acrylic polymeric material. Typically,
the bone cement is comprised of two components: a dry power component and
a liquid component, which are subsequently mixed together. The dry
component generally includes an acrylic polymer, such as
polymethylmethacrylate (PMMA). The dry component can also contain a
polymerization initiator such as benzoylperoxide, which initiates the
free-radical polymerization process that occurs when the bone cement is
formed. The liquid component, on the other hand, generally contains a
liquid monomer such as methyl methacrylate (MMA). The liquid component
can also contain an accelerator such as an amine (e.g.,
N,N-dimethyl-p-toluidine). A stabilizer, such as hydroquinone, can also
be added to the liquid component to prevent premature polymerization of
the liquid monomer. When the liquid component is mixed with the dry
component, the dry component begins to dissolve or swell in the liquid
monomer. The amine accelerator reacts with the initiator to form free
radicals that begin to link monomer units to form polymer chains. In the
next two to four minutes, the polymerization process proceeds changing
the viscosity of the mixture from a syrup-like consistency (low
viscosity) into a dough-like consistency (high viscosity). Ultimately,
further polymerization and curing occur, causing the cement to harden and
affix a prosthesis to a bone.

[0158]In certain aspects of the invention, bone cement 955 or another
liquid attachment material such as injectable calciumhydroxyapatite can
be injected into the marrow cavity through one or more openings 950 in
the prosthesis. These openings in the prosthesis can extend from the
articular surface to the undersurface of the prosthesis 960. After
injection, the openings can be closed with a polymer, silicon, metal,
metal alloy or bioresorbable plug.

[0159]In another embodiment, one or more components of the articular
surface repair (e.g., the surface of the system that is pointing towards
the underlying bone or bone marrow) can be porous or porous coated. A
variety of different porous metal coatings have been proposed for
enhancing fixation of a metallic prosthesis by bone tissue ingrowth.
Thus, for example, U.S. Pat. No. 3,855,638 discloses a surgical
prosthetic device, which may be used as a bone prosthesis, comprising a
composite structure consisting of a solid metallic material substrate and
a porous coating of the same solid metallic material adhered to and
extending over at least a portion of the surface of the substrate. The
porous coating consists of a plurality of small discrete particles of
metallic material bonded together at their points of contact with each
other to define a plurality of connected interstitial pores in the
coating. The size and spacing of the particles, which can be distributed
in a plurality of monolayers, can be such that the average interstitial
pore size is not more than about 200 microns. Additionally, the pore size
distribution can be substantially uniform from the substrate-coating
interface to the surface of the coating. In another embodiment, the
articular surface repair system can contain one or more polymeric
materials that can be loaded with and release therapeutic agents
including drugs or other pharmacological treatments that can be used for
drug delivery. The polymeric materials can, for example, be placed inside
areas of porous coating. The polymeric materials can be used to release
therapeutic drugs, e.g. bone or cartilage growth stimulating drugs. This
embodiment can be combined with other embodiments, wherein portions of
the articular surface repair system can be bioresorbable. For example,
the superficial layer of an articular surface repair system or portions
of its superficial layer can be bioresorbable. As the superficial layer
gets increasingly resorbed, local release of a cartilage
growth-stimulating drug can facilitate ingrowth of cartilage cells and
matrix formation.

[0160]In any of the methods or compositions described herein, the
articular surface repair system can be pre-manufactured with a range of
sizes, curvatures and thicknesses. Alternatively, the articular surface
repair system can be custom-made for an individual patient.

[0161]2.8 Sizing

[0162]The articular repair system may be formed or selected so that it
will achieve a near anatomic fit or match with the surrounding or
adjacent cartilage or subchondral bone or menisci and other tissue. The
shape of the repair system can be based on the analysis of an electronic
image (e.g. MRI, CT, digital tomosynthesis, optical coherence tomography
or the like). If the articular repair system is intended to replace an
area of diseased cartilage or lost cartilage, the near anatomic fit can
be achieved using a method that provides a virtual reconstruction of the
shape of healthy cartilage in an electronic image.

[0163]In one embodiment of the invention, a near normal cartilage surface
at the position of the cartilage defect may be reconstructed by
interpolating the healthy cartilage surface across the cartilage defect
or area of diseased cartilage. This can, for example, be achieved by
describing the healthy cartilage by means of a parametric surface (e.g. a
B-spline surface), for which the control points are placed such that the
parametric surface follows the contour of the healthy cartilage and
bridges the cartilage defect or area of diseased cartilage. The
continuity properties of the parametric surface will provide a smooth
integration of the part that bridges the cartilage defect or area of
diseased cartilage with the contour of the surrounding healthy cartilage.
The part of the parametric surface over the area of the cartilage defect
or area of diseased cartilage can be used to determine the shape or part
or the shape of the articular repair system to match with the surrounding
cartilage.

[0164]In another embodiment, a near normal cartilage surface at the
position of the cartilage defect or area of diseased cartilage may be
reconstructed using morphological image processing. In a first step, the
cartilage can be extracted from the electronic image using manual,
semi-automated and/or automated segmentation techniques (e.g., manual
tracing, region growing, live wire, model-based segmentation), resulting
in a binary image. Defects in the cartilage appear as indentations that
may be filled with a morphological closing operation performed in 2-D or
3-D with an appropriately selected structuring element. The closing
operation is typically defined as a dilation followed by an erosion. A
dilation operator sets the current pixel in the output image to 1 if at
least one pixel of the structuring element lies inside a region in the
source image. An erosion operator sets the current pixel in the output
image to 1 if the whole structuring element lies inside a region in the
source image. The filling of the cartilage defect or area of diseased
cartilage creates a new surface over the area of the cartilage defect or
area of diseased cartilage that can be used to determine the shape or
part of the shape of the articular repair system to match with the
surrounding cartilage or subchondral bone.

[0165]As described above, the articular repair system may be formed or
selected from a library or database of systems of various sizes,
curvatures and thicknesses so that it will achieve a near anatomic fit or
match with the surrounding or adjacent cartilage and/or subchondral bone.
These systems can be pre-made or made to order for an individual patient.
In order to control the fit or match of the articular repair system with
the surrounding or adjacent cartilage or subchondral bone or menisci and
other tissues preoperatively, a software program may be used that
projects the articular repair system over the anatomic position where it
will be implanted. Suitable software may be commercially available and/or
readily modified or designed by a skilled programmer.

[0166]In yet another embodiment, the articular surface repair system may
be projected over the implantation site using one or more 3-D images. The
cartilage and/or subchondral bone and other anatomic structures are
extracted from a 3-D electronic image such as an MRI or a CT using
manual, semi-automated and/or automated segmentation techniques. A 3-D
representation of the cartilage and/or subchondral bone and other
anatomic structures as well as the articular repair system is generated,
for example using a polygon or NURBS surface or other parametric surface
representation. For a description of various parametric surface
representations see, for example Foley, J. D. et al., Computer Graphics:
Principles and Practice in C; Addison-Wesley, 2nd edition, 1995).
The 3-D representations of the cartilage and/or subchondral bone and
other anatomic structures and the articular repair system can be merged
into a common coordinate system. The articular repair system can then be
placed at the desired implantation site. The representations of the
cartilage, subchondral bone, menisci and other anatomic structures and
the articular repair system are rendered into a 3-D image, for example
application programming interfaces (APIs) OpenGL® (standard library
of advanced 3-D graphics functions developed by SGI, Inc.; available as
part of the drivers for PC-based video cards, for example from
www.nvidia.com for NVIDIA video cards or www.3dlabs.com for 3Dlabs
products, or as part of the system software for Unix workstations) or
DirectX® (multimedia API for Microsoft Windows® based PC systems;
available from www.microsoft.com). The 3-D image may be rendered showing
the cartilage, subchondral bone, menisci or other anatomic objects, and
the articular repair system from varying angles, e.g. by rotating or
moving them interactively or non-interactively, in real-time or
non-real-time. The software can be designed so that the articular repair
system with the best fit relative to the cartilage and/or subchondral
bone is automatically selected, for example using some of the techniques
described above. Alternatively, the operator can select an articular
repair system and project it or drag it onto the implantation site using
suitable tools and techniques. The operator can move and rotate the
articular repair systems in three dimensions relative to the implantation
site and can perform a visual inspection of the fit between the articular
repair system and the implantation site. The visual inspection can be
computer assisted. The procedure can be repeated until a satisfactory fit
has been achieved. The procedure can be entirely manual by the operator;
it can, however, also be computer-assisted. For example, the software may
select a first trial implant that the operator can test. The operator can
evaluate the fit. The software can be designed and used to highlight
areas of poor alignment between the implant and the surrounding cartilage
or subchondral bone or menisci or other tissues. Based on this
information, the software or the operator can select another implant and
test its alignment. One of skill in the art will readily be able to
select, modify and/or create suitable computer programs for the purposes
described herein.

[0167]In another embodiment, the implantation site may be visualized using
one or more cross-sectional 2-D images. Typically, a series of 2-D
cross-sectional images will be used. The 2-D images can be generated with
imaging tests such as CT, MRI, digital tomosynthesis, ultrasound, or
optical coherence tomography using methods and tools known to those of
skill in the art. The articular repair system can then be superimposed
onto one or more of these 2-D images. The 2-D cross-sectional images can
be reconstructed in other planes, e.g. from sagittal to coronal, etc.
Isotropic data sets (e.g., data sets where the slice thickness is the
same or nearly the same as the in-plane resolution) or near isotropic
data sets can also be used. Multiple planes can be displayed
simultaneously, for example using a split screen display. The operator
can also scroll through the 2-D images in any desired orientation in real
time or near real time; the operator can rotate the imaged tissue volume
while doing this. The articular repair system can be displayed in
cross-section utilizing different display planes, e.g. sagittal, coronal
or axial, typically matching those of the 2-D images demonstrating the
cartilage, subchondral bone, menisci or other tissue. Alternatively, a
three-dimensional display can be used for the articular repair system.
The 2-D electronic image and the 2-D or 3-D representation of the
articular repair system can be merged into a common coordinate system.
The cartilage repair system can then be placed at the desired
implantation site. The series of 2-D cross-sections of the anatomic
structures, the implantation site and the articular repair system may be
displayed interactively (e.g. the operator can scroll through a series of
slices) or non-interactively (e.g. as an animation that moves through the
series of slices), in real-time or non-real-time.

[0168]The software can be designed so that the articular repair system
with the best fit relative to the cartilage and/or subchondral bone is
automatically selected, for example using one or more of the techniques
described above. Alternatively, the operator can select an articular
repair system and project it or drag it onto the implantation site
displayed on the cross-sectional 2-D images. The operator can move and
rotate the articular repair system relative to the implantation site and
scroll through a cross-sectional 2-D display of the articular repair
system and of the anatomic structures. The operator can perform a visual
and/or computer-assisted inspection of the fit between the articular
repair system and the implantation site. The procedure can be repeated
until a satisfactory fit has been achieved. The procedure can be entirely
manual by the operator; it can, however, also be computer-assisted. For
example, the software may select a first trial implant that the operator
can test (e.g., evaluate the fit). Software that highlights areas of poor
alignment between the implant and the surrounding cartilage or
subchondral bone or menisci or other tissues can also be designed and
used. Based on this information, the software or the operator can select
another implant and test its alignment.

[0169]3.0 Implantation

[0170]Following one or more manipulations (e.g., shaping, growth,
development, etc), the cartilage replacement or regenerating material can
then be implanted into the area of the defect. Implantation can be
performed with the cartilage replacement or regenerating material still
attached to the base material or removed from the base material. Any
suitable methods and devices may be used for implantation, for example,
devices as described in U.S. Pat. Nos. 6,375,658; 6,358,253; 6,328,765;
and International Publication WO 01/19254.

[0171]In selected cartilage defects, the implantation site can be prepared
with a single cut across the articular surface (FIG. 10). In this case,
single 1010 and multi-component 1020 prostheses can be utilized.

[0172]3.1 Surgical Tools

[0173]Further, surgical assistance can be provided by using a device
applied to the outer surface of the articular cartilage or the bone in
order to match the alignment of the articular repair system and the
recipient site or the joint. The device can be round, circular, oval,
ellipsoid, curved or irregular in shape. The shape can be selected or
adjusted to match or enclose an area of diseased cartilage or an area
slightly larger than the area of diseased cartilage. Alternatively, the
device can be designed to be substantially larger than the area of
diseased cartilage. Such devices are typically preferred when replacement
of a majority or an entire articular surface is contemplated.

[0174]Mechanical devices can be used for surgical assistance (e.g.,
surgical tools), for example using gels, molds, plastics or metal. One or
more electronic images can be obtained providing object coordinates that
define the articular and/or bone surface and shape. These objects
coordinates can be utilized to either shape the device, e.g. using a
CAD/CAM technique, to be adapted to a patient's articular anatomy or,
alternatively, to select a typically pre-made device that has a good fit
with a patient's articular anatomy. The device can have a surface and
shape that will match all or portions of the articular or bone surface
and shape, e.g. similar to a "mirror image." The device can include
apertures, slots and/or holes to accommodate surgical instruments such as
drills and saws. Typically, a position will be chosen that will result in
an anatomically desirable cut plane or drill hole orientation for
subsequent placement of an articular repair system. Moreover, the device
can be designed so that the depth of the drill can be controlled, e.g.,
the drill cannot go any deeper into the tissue than defined by the
thickness of the device, and the size of the hole in block can be
designed to essentially match the size of the implant. Information about
other joints or axis and alignment information of a joint or extremity
can be included when selecting the position of these slots or holes.

[0175]In certain embodiments, the surgical assistance device comprises an
array of adjustable, closely spaced pins (e.g., plurality of individually
moveable mechanical elements). One or more electronic images can be
obtained providing object coordinates that define the articular and/or
bone surface and shape. These objects coordinates can be entered or
transferred into the device, for example manually or electronically, and
the information can be used to create a surface and shape that will match
all or portions of the articular and/or bone surface and shape by moving
one or more of the elements, e.g. similar to a "mirror image." The device
can include slots and holes to accommodate surgical instruments such as
drills and saws. The position of these slots and holes can be adjusted by
moving one or more of the mechanical elements. Typically, a position will
be chosen that will result in an anatomically desirable cut plane or
drill hole orientation for subsequent placement of an articular repair
system. Information about other joints or axis and alignment information
of a joint or extremity can be included when selecting the position of
these slots or holes.

[0176]In another embodiment, a frame can be applied to the bone or the
cartilage in areas other than the diseased bone or cartilage. The frame
can include holders and guides for surgical instruments. The frame can be
attached to one or preferably more previously defined anatomic reference
points. Alternatively, the position of the frame can be cross-registered
relative to one, preferably more anatomic landmarks, using an imaging
test, for example one or more fluoroscopic images acquired
intraoperatively. One or more electronic images can be obtained providing
object coordinates that define the articular and/or bone surface and
shape. These objects coordinates can be entered or transferred into the
device, for example manually or electronically, and the information can
be used to move one or more of the holders or guides for surgical
instruments. Typically, a position will be chosen that will result in a
surgically or anatomically desirable cut plane or drill hole orientation
for subsequent placement of an articular repair system. Information about
other joints or axis and alignment information of a joint or extremity
can be included when selecting the position of these slots or holes.

[0177]For example, when a total knee arthroplasty is contemplated, the
patient can undergo an imaging test that will demonstrate the articular
anatomy of a knee joint, e.g. width of the femoral condyles, the tibial
plateau etc. Additionally, other joints can be included in the imaging
test thereby yielding information on femoral and tibial axes, deformities
such as varus and valgus and other articular alignment. The imaging test
can be an x-ray image, preferably in standing, load-bearing position, a
CT scan or an MRI scan or combinations thereof. The articular surface and
shape as well as alignment information generated with the imaging test
can be used to shape the surgical assistance device or can be entered
into the surgical assistance device and can be used to define the
preferred location and orientation of saw guides or drill holes or guides
for reaming devices. Intraoperatively, the surgical assistance device is
applied to the femoral condyle(s) and subsequently the tibial plateau(s)
by matching its surface with the articular surface or by attaching it to
anatomic reference points on the bone or cartilage. The surgeon can then
introduce a saw through the saw guides and prepare the joint for the
implantation. By cutting the cartilage and bone along anatomically
defined planes, a more reproducible placement of the implant can be
achieved. This can ultimately result in improved postoperative results by
optimizing biomechanical stresses applied to the implant and surrounding
bone for the patient's anatomy.

[0178]Thus, surgical tools described herein may also be designed and used
to control drill alignment, depth and width, for example when preparing a
site to receive an implant. (See, FIGS. 13, 15 and 16). For example, the
tools described herein, which typically conform to the joint surface, may
provide for improved drill alignment and more accurate placement of any
implant. An anatomically correct tool can be constructed by a number of
methods and may be made of any material, preferably a translucent
material such as plastic, lucite, silastic, SLA or the like, and
typically is a block-like shape prior to molding.

[0179]Furthermore, re-useable tools (e.g., molds) may be also be created
and employed. Non-limiting examples of re-useable materials include
putties and other deformable materials (e.g., an array of adjustable
closely spaced pins that can be configured to match the topography of a
joint surface). In these embodiments, the mold may be created directly
from the joint during surgery or, alternatively, created from an image of
the joint, for example, using one or more computer programs to determine
object coordinates defining the surface contour of the joint and
transferring (e.g., dialing-in) these coordinates to the tool.
Subsequently, the tool can be aligned accurately over the joint and,
accordingly, the drill and implant will be more accurately placed in and
over the articular surface.

[0180]In both single-use and re-useable embodiments, the tool can be
designed so that the depth of the block controls the depth of the drill,
i.e., the drill cannot go any deeper into the tissue than the depth of
block, and the size of the hole in block can be designed to essentially
match the size of the implant. The tool can be used for general
prosthesis implantation, including, but not limited to, the articular
repair implants described herein and for reaming the marrow in the case
of a total arthroplasty.

[0181]These surgical tools (devices) can also be used to remove an area of
diseased cartilage and underlying bone or an area slightly larger than
the diseased cartilage and underlying bone. In addition, the device can
be used on a "donor," e.g., a cadaveric specimen to obtain implantable
repair material. The device is typically positioned in the same general
anatomic area in which the tissue was removed in the recipient. The shape
of the device is then used to identify a donor site providing a seamless
or near seamless match between the donor tissue sample and the recipient
site. This is achieved by identifying the position of the device in which
the articular surface in the donor, e.g. a cadaveric specimen has a
seamless or near seamless contact with the inner surface when applied to
the cartilage.

[0182]The device can be molded, machined or formed based on the size of
the area of diseased cartilage and based on the curvature of the
cartilage or the underlying subchondral bone or a combination of both.
The device can then be applied to the donor, (e.g., a cadaveric specimen)
and the donor tissue can be obtained with use of a blade or saw or other
tissue cutting device. The device can then be applied to the recipient in
the area of the diseased cartilage and the diseased cartilage and
underlying bone can be removed with use of a blade or saw or other tissue
cutting device whereby the size and shape of the removed tissue
containing the diseased cartilage will closely resemble the size and
shape of the donor tissue. The donor tissue can then be attached to the
recipient site. For example, said attachment can be achieved with use of
screws or pins (e.g., metallic, non-metallic or bioresorable) or other
fixation means including but not limited to a tissue adhesive. Attachment
can be through the cartilage surface or alternatively, through the marrow
space.

[0183]The implant site can be prepared with use of a robotic device. The
robotic device can use information from an electronic image for preparing
the recipient site.

[0184]Identification and preparation of the implant site and insertion of
the implant can be supported by an image-guided surgery system (surgical
navigation system). In such a system, the position or orientation of a
surgical instrument with respect to the patient's anatomy is tracked in
real-time in one or more 2D or 3D images. These 2D or 3D images can
images or can be calculated from images that were acquired
preoperatively, such as MR or CT images. The position and orientation of
the surgical instrument is determined from markers attached to the
instrument. These markers can be located by a detector using, for
example, optical, acoustical or electromagnetic signals.

[0185]Identification and preparation of the implant site and insertion of
the implant can also be supported with use of a C-arm system. The C-arm
system can afford imaging of the joint in one or, more preferred,
multiple planes. The multiplanar imaging capability can aid in defining
the shape of an articular surface. This information can be used to
selected an implant with a good fit to the articular surface. Currently
available C-arm systems also afford cross-sectional imaging capability,
for example for identification and preparation of the implant site and
insertion of the implant. C-arm imaging can be combined with
administration of radiographic contrast.

[0186]In still other embodiments, the surgical devices described herein
can include one or more materials that harden to form a mold of the
articular surface. A wide-variety of materials that harden in situ have
been described including polymers that can be triggered to undergo a
phase change, for example polymers that are liquid or semi-liquid and
harden to solids or gels upon exposure to air, application of ultraviolet
light, visible light, exposure to blood, water or other ionic changes.
(See, also, U.S. Pat. No. 6,443,988 and documents cited therein).
Non-limiting examples of suitable curable and hardening materials include
polyurethane materials (e.g., U.S. Pat. Nos. 6,443,988, 5,288,797,
4,098,626 and 4,594,380; and Lu et al. (2000) BioMaterials
21(15):1595-1605 describing porous poly(L-lactide acid foams);
hydrophilic polymers as disclosed, for example, in U.S. Pat. No.
5,162,430; hydrogel materials such as those described in Wake et al.
(1995) Cell Transplantation 4(3):275-279, Wiese et al. (2001) J.
Biomedical Materials Research 54(2):179-188 and Marler et al. (2000)
Plastic Reconstruct. Surgery 105(6):2049-2058; hyaluronic acid materials
(e.g., Duranti et al. (1998) Dermatologic Surgery 24(12):1317-1325);
expanding beads such as chitin beads (e.g., Yusof et al. (2001) J.
Biomedical Materials Research 54(1):59-68); and/or materials used in
dental applications (See, e.g., Brauer and Antonucci, "Dental
Applications" pp. 257-258 in "Concise Encyclopedia of Polymer Science and
Engineering" and U.S. Pat. No. 4,368,040). Any biocompatible material
that is sufficiently flowable to permit it to be delivered to the joint
and there undergo complete cure in situ under physiologically acceptable
conditions can be used. The material may also be biodegradable.

[0187]The curable materials can be used in conjunction with a surgical
tool as described herein. For example, the surgical tool may include one
or more apertures therein adapted to receive injections and the curable
materials can be injected through the apertures. Prior to solidifying in
situ the materials will conform to the articular surface facing the
surgical tool and, accordingly, will form a mirror image impression of
the surface upon hardening thereby recreating a normal or near normal
articular surface. In addition, curable materials or surgical tools can
also be used in conjunction with any of the imaging tests and analysis
described herein, for example by molding these materials or surgical
tools based on an image of a joint.

[0188]4.0 Kits

[0189]Also described herein are kits comprising one or more of the
methods, systems and/or compositions described herein. In particular, a
kit may include one or more of the following: instructions (methods) of
obtaining electronic images; systems or instructions for evaluating
electronic images; one or more computer means capable of analyzing or
processing the electronic images; and/or one or more surgical tools for
implanting an articular repair system. The kits may include other
materials, for example, instructions, reagents, containers and/or imaging
aids (e.g., films, holders, digitizers, etc.).

[0190]The following examples are included to more fully illustrate the
present invention. Additionally, these examples provide preferred
embodiments of the invention and are not meant to limit the scope
thereof.

EXAMPLE 1

Design and Construction of a Three-Dimensional Articular Repair System

[0191]Areas of cartilage are imaged as described herein to detect areas of
cartilage loss and/or diseased cartilage. The margins and shape of the
cartilage and subchondral bone adjacent to the diseased areas are
determined. The thickness of the cartilage is determined. The size of the
articular repair system is determined based on the above measurements.
(FIGS. 12-14). In particular, the repair system is either selected (based
on best fit) from a catalogue of existing, pre-made implants with a range
of different sizes and curvatures or custom-designed using CAD/CAM
technology. The library of existing shapes is typically on the order of
about 30 sizes.

[0192]The implant is a chromium cobalt implant (see also FIGS. 12-14 and
17-19). The articular surface is polished and the external dimensions
slightly greater than the area of diseased cartilage. The shape is
adapted to achieve perfect or near perfect joint congruity utilizing
shape information of surrounding cartilage and underlying subchondral
bone. Other design features of the implant may include: a slanted (60- to
70-degree angle) interface to adjacent cartilage; a broad-based base
component for depth control; a press fit design of base component; a
porous coating of base component for ingrowth of bone and rigid
stabilization; a dual peg design for large defects implant stabilization,
also porous coated (FIG. 12A); a single stabilizer strut with tapered,
four fin and step design for small, focal defects, also porous coated
(FIG. 12B); and a design applicable to femoral resurfacing (convex
external surface) and tibial resurfacing (concave external surface).

[0195]The articular repair systems are inserted using arthroscopic
assistance. The device does not require the 15 to 30 cm incision utilized
in unicompartmental and total knee arthroplasties. The procedure is
performed under regional anesthesia, typically epidural anesthesia. The
surgeon may apply a tourniquet on the upper thigh of the patient to
restrict the blood flow to the knee during the procedure. The leg is
prepped and draped in sterile technique. A stylette is used to create two
small 2 mm ports at the anteromedial and the anterolateral aspect of the
joint using classical arthroscopic technique. The arthroscope is inserted
via the lateral port. The arthroscopic instruments are inserted via the
medial port. The cartilage defect is visualized using the arthroscope. A
cartilage defect locator device is placed inside the diseased cartilage.
The probe has a U-shape, with the first arm touching the center of the
area of diseased cartilage inside the joint and the second arm of the U
remaining outside the joint. The second arm of the U indicates the
position of the cartilage relative to the skin. The surgeon marks the
position of the cartilage defect on the skin. A 3 cm incision is created
over the defect. Tissue retractors are inserted and the defect is
visualized.

[0196]A translucent Lucite block matching the 3D shape of the adjacent
cartilage and the cartilage defect is placed over the cartilage defect
(FIG. 13). For larger defects, the Lucite block includes a lateral slot
for insertion of a saw. The saw is inserted and a straight cut is made
across the articular surface, removing an area slightly larger than the
diseased cartilage. The center of the Lucite block contains two drill
holes with a 7.2 mm diameter. A 7.1 mm drill with drill guide controlling
the depth of tissue penetration is inserted via the drill hole. Holes for
the cylindrical pegs of the implant are created. The drill and the Lucite
block are subsequently removed.

[0197]A plastic model/trial implant of the mini-repair system matching the
outer dimensions of the implant is then inserted. The trial implant is
utilized to confirm anatomic placement of the actual implant. If
indicated, the surgeon can make smaller adjustments at this point to
improve the match, e.g. slight expansion of the drill holes or adjustment
of the cut plane.

[0198]The implant is then inserted with the pegs pointing into the drill
holes. Anterior and posterior positions of the implant are color-coded;
specifically the anterior peg is marked with a red color and a small
letter "A", while the posterior peg has a green color and a small letter
"P". Similarly, the medial aspect of the implant is color-coded yellow
and marked with a small letter "M" and the lateral aspect of the implant
is marked with a small letter "L". The Lucite block is then placed on the
external surface of the implant and a plastic hammer is used to gently
advance the pegs into the drill holes. The pegs are designed to achieve a
press fit.

[0199]The same technique can be applied in the tibia. The implant has a
concave articular surface matching the 3D shape of the tibial plateau.
Immediate stabilization of the device can be achieved by combining it
with bone cement if desired.

[0200]B. Small, Focal Cartilage Defect

[0201]After identification of the cartilage defect and marking of the skin
surface using the proprietary U-shaped cartilage defect locator device as
described herein, a 3 cm incision is placed and the tissue retractors are
inserted. The cartilage defect is visualized.

[0202]A first Lucite block matching the 3D surface of the femoral condyle
is placed over the cartilage defect. The central portion of the Lucite
block contains a drill hole with an inner diameter of, for example, 1.5
cm, corresponding to the diameter of the base plate of the implant. A
standard surgical drill with a drill guide for depth control is inserted
through the Lucite block, and the recipient site is prepared for the base
component of the implant. The drill and the Lucite block are then
removed.

[0203]A second Lucite block of identical outer dimensions is then placed
over the implant recipient site. The second Lucite block has a rounded,
cylindrical extension matching the size of the first drill hole (and
matching the shape of the base component of the implant), with a diameter
0.1 mm smaller than the first drill hole and 0.2 mm smaller than that of
the base of the implant. The cylindrical extension is placed inside the
first drill hole.

[0204]The second Lucite block contains a drill hole extending from the
external surface of the block to the cylindrical extension. The inner
diameter of the second drill hole matches the diameter of the distal
portion of the fin-shaped stabilizer strut of the implant, e.g. 3 mm. A
drill, e.g. with 3 mm diameter, with a drill guide for depth control is
inserted into the second hole and the recipient site is prepared for the
stabilizer strut with four fin and step design. The drill and the Lucite
block are then removed.

[0205]A plastic model/trial implant matching the 3-D shape of the final
implant with a diameter of the base component of 0.2 mm less than that of
the final implant and a cylindrical rather than tapered strut stabilizer
with a diameter of 0.1 mm less than the distal portion of the final
implant is then placed inside the cartilage defect. The plastic
model/trial implant is used to confirm alignment of the implant surface
with the surrounding cartilage. The surgeon then performs final
adjustments.

[0206]The implant is subsequently placed inside the recipient site. The
anterior fin of the implant is marked with red color and labeled "A." The
posterior fin is marked green with a label "P" and the medial fin is
color coded yellow with a label "M." The Lucite block is then placed over
the implant. A plastic hammer is utilized to advance the implant slowly
into the recipient site. A press fit is achieved with help of the tapered
and four fin design of the strut, as well as the slightly greater
diameter (0.1 mm) of the base component relative to the drill hole. The
Lucite block is removed. The tissue retractors are then removed. Standard
surgical technique is used to close the 3 cm incision. The same procedure
described above for the medial femoral condyle can also be applied to the
lateral femoral condyle, the medial tibial plateau, the lateral tibial
plateau and the patella. Immediate stabilization of the device can be
achieved by combining it with bone cement if desired.